Runx1 Messenger RNA Delivered by Polyplex Nanomicelles Alleviate Spinal Disc Hydration Loss in a Rat Disc Degeneration Model

Vertebral disc degenerative disease (DDD) affects millions of people worldwide and is a critical factor leading to low back and neck pain and consequent disability. Currently, no strategy has addressed curing DDD from fundamental aspects, because the pathological mechanism leading to DDD is still controversial. One possible mechanism points to the homeostatic status of extracellular matrix (ECM) anabolism, and catabolism in the disc may play a vital role in the disease’s progression. If the damaged disc receives an abundant amount of cartilage, anabolic factors may stimulate the residual cells in the damaged disc to secrete the ECM and mitigate the degeneration process. To examine this hypothesis, a cartilage anabolic factor, Runx1, was expressed by mRNA through a sophisticated polyamine-based PEG-polyplex nanomicelle delivery system in the damaged disc in a rat model. The mRNA medicine and polyamine carrier have favorable safety characteristics and biocompatibility for regenerative medicine. The endocytosis of mRNA-loaded polyplex nanomicelles in vitro, mRNA delivery efficacy, hydration content, disc shrinkage, and ECM in the disc in vivo were also examined. The data revealed that the mRNA-loaded polyplex nanomicelle was promptly engulfed by cellular late endosome, then spread into the cytosol homogeneously at a rate of less than 20 min post-administration of the mRNA medicine. The mRNA expression persisted for at least 6-days post-injection in vivo. Furthermore, the Runx1 mRNA delivered by polyplex nanomicelles increased hydration content by ≈43% in the punctured disc at 4-weeks post-injection (wpi) compared with naked Runx1 mRNA administration. Meanwhile, the disc space and ECM production were also significantly ameliorated in the polyplex nanomicelle group. This study demonstrated that anabolic factor administration by polyplex nanomicelle-protected mRNA medicine, such as Runx1, plays a key role in alleviating the progress of DDD, which is an imbalance scenario of disc metabolism. This platform could be further developed as a promising strategy applied to regenerative medicine.

An Observational Study to Assess Samprapti Ghataka in Cervical Spondylosis with Special Reference to Radiological Findings

The western lifestyle, characterized by convenience food, television and PC’s taking its all on children as well as adults and is producing increased number of overweight, passive youngsters with lifestyle diseases. Spondylosis is degenerative inter vertebral disc with secondary proliferative osteoarthritis. Disc spaces collapse and associated ligament thickening and bony proliferation result in nerve root compression and narrowing of spinal canal. Cervical spondylosis which is a degenerative disorder in which structural and also functional derangements take place. It is an age related and also work-related disability usually found in the 30-60 years of age group. According to Ayurveda it is one among the Vataja Nanatmaja Vikara. There is no exact clinical entity mentioned in classics like cervical spondylosis, but it can be compared to Greevastambha, Apabahuka, Vishwachi Manyastamba, Manyagraha, Shirograham, Greevahundanam, Greevasandhigatavata. Cervical Spondylosis also known as cervical osteoarthritis or neck arthritis, is a common age-related condition that affects the joints and discs in our neck.

Bending rod is unnecessary in single-level posterior internal fixation and fusion in treatment of lumbar degenerative diseases

Background Bending rod is a routine in lumbar fusion and fixation surgery, but there is no study investigating whether bending rod in one level is necessary. Methods Patients receiving 1 level lumbar fixation and fusion between May 2018 and September 2020 were included with a minimum 6-month follow-up. The routine of bending rod was omitted during fixation. Preoperative and postoperative radiological parameters were compared. Results There were 67 patients included in the study. Segment lordosis angle increased obviously from 10° (1–39°) to 14° (2–30°) immediately after operation (p = 0.000). T5-T12 increased from 22.97 ± 12.31° to 25.52 ± 11.83° by the 3rd months after surgery (p = 0.011). SS decreased from 35.45 ± 10.47 to 32.19 ± 11.37 in 6-month follow-up (p = 0.038), and PI dropped from 56.97 ± 14.24 to 53.19 ± 12.84 (p = 0.016). ROM of SLA decreased from 4.13 ± 3.14° to 1.93 ± 1.87° at that time point (p = 0.028). Those changes were not seen at 12-month follow-up. No evidence of adjacent vertebral disc degeneration was observed at any time point. Conclusions No sagittal imbalance, dynamic instability or adjacent vertebral degeneration was observed by the 12th month after single-segment posterior lumbar fusion with the use of unbent rods. Bending rod could be omitted in 1-level lumbar fusion to simplify the procedure and reduce operating time.

P066 Orthopedic complications of osteogenesis imperfecta

Background Osteogenesis imperfecta (OI) is an inherited connective tissue disorder including various skeletal manifestations. Bone fragility, vertebral body malformation and length lower limbs inequality are often responsible for orthopedic complications. The aim of our study was to determine orthopedic complications of OI and to specify management modalities in rheumatology. Methods We conduct a retrospective study based on the files of children referred to the rheumatology departement over the last 15 years, for treatment of OI. The evaluation was clinical and radiological. Clinical examination included joint and spine assessment. An X-ray of the spine and painful joints associated with a quantitative densitometry were requested. Results Five patients were collected, their mean age was 9 years. All patients had peripheral fracture. Joint assessment revealed a flessum of the elbow and a reduction of the motion of hip in 40% of cases. Scoliosis was noted also in 40% of cases. The average of spine Z –score was -3, 4. All children had benefited from oral calcium and vitamin D supplementation associated with cyclic intravenous bisphosphonates and an adapted rehabilitation protocol. Surgical management was often needed in 2 cases. Discussion and Conclusion Orthopedic complications during OI are essentially the consequence of lower bone mineral density which would cause peripheral or vertebral fracture. Indeed, some other factors like length inequality, pelvic obliquity, ligamentous laxity and inter-vertebral disc abnormalities could be involved in scoliotic progression. The management of these skeletal complications must be early and multidisciplinary in order to improve the prognosis and the quality of life of the patient

Regional distribution of computed tomography attenuation across the lumbar endplate

The vertebral endplate forms a structural boundary between intervertebral disc and the trabecular bone of the vertebral body. As a mechanical interface between the stiff bone and resilient disc, the endplate is the weakest portion of the vertebral-disc complex and is predisposed to mechanical failure. However, the literature concerning the bone mineral density (BMD) distribution within the spinal endplate is comparatively sparse. The objective of this study is to investigate the three-dimensional (3D) distribution of computed tomography (CT) attenuation across the lumbosacral endplate measured in Hounsfield Units (HU). A total of 308 endplates from 28 cadaveric fresh-frozen lumbosacral spines were used in this study. Each spine was CT-scanned and the resulting DICOM data was used to obtain HU values of the bone endplate. Each individual endplate surface was subdivided into five clinically-relevant topographic zones. Attenuation was analyzed by spinal levels, sites (superior or inferior endplate) and endplate region. The highest HU values were found at the S1 endplate. Comparisons between the superior and inferior endplates showed the HU values in inferior endplates were significantly higher than those in the superior endplates within the same vertebra and the HU values in endplates cranial to the disc were significantly higher than those in the endplates caudal to the disc within the same disc. Attenuation in the peripheral region was significantly higher than in the central region by 32.5%. Regional comparison within the peripheral region showed the HU values in the posterior region were significantly higher than those in the anterior region and the HU values in the left region were significantly higher than those in the right region. This study provided detailed data on the regional HU distribution across the lumbosacral endplate, which can be useful to understand causes of some endplate lesions, such as fracture, and also to design interbody instrumentation.

Structural features of the intervertebral disc in rats

The aim of our work was to study the structural organization of the components of vertebral disc of rats on the microscopic level in the normal state.This goal was achieved by means of microscopic method of visualization of cellular components of the intervertebral disc of rats. Histological preparations were made in accordance with the conventional method of using the dye hematoxylin, eosin and azan according to the method of Heidenhain, PAS reaction according to MacManus and Alcian blue according to Steedman.As a result of the microstructural study, it was ascertained that the rat’s intervertebral disc normally consists of a gelatinous (pulpal) nucleus and a fibrous ring. It is separated from the vertebral bodies by a thin layer of cartilaginous tissue of the locking plates and hyaline cartilage, which covers the bodies of adjacent vertebrae. The data that rats do not have locking plates can be rarely found in the literature. The vessels verging the intervertebral disc radially -in front, back and from the sides, branch out from the vessels of vertebral periosteum. In the cartilaginous tissue of intervertebral disc, vessels are not visualized.

Effect of single and multilevel artificial inter-vertebral disc replacement in lumbar spine: A finite element study

Degenerative disc disease (DDD) in lumbar spine is one of the major musculoskeletal disorders that cause low back pain (LBP). The intervertebral disc structure and dynamics of the lumbar spine are significantly affected by lumbar DDD, leading to a reduced range of motion (ROM), muscle weakness and gradual degradation. Spinal fusion and inter-vertebral disc replacement prostheses are two major surgical methods used for treating lumbar DDD. The aim of this present study is to examine biomechanical impacts of single level (L3-L4 and L4-L5) and multi level (L3-L4-L5) inter-vertebral disc replacement in lumbar spine (L2-L5) and to compare the performance with intact spine. Finite element (FE) analysis has been used to compare the mobility and stress distribution of all the models for four physiological movements, namely flexion, extension, left and right lateral bending under 6, 8 and 10 Nm moments. Spinal fusion implants completely restrict the motion of the implanted segment and increase disc stress at the adjacent levels. In contrast to that, the results single level ADR models showed closer ROM and disc stress to natural model. At the spinal segments adjacent to the implantation, single level ADR shows lower chance of disc degeneration. However, significantly increased ROM was observed in case of double level ADR.

An Independent Agreement Study of Modified Pfirrmann Grading System for Cervical Inter-vertebral Disc Degeneration in Cervical Spondylotic Myelopathy

Background Neck pain, sensory disturbance and motor dysfunction in most patients suffered cervical spondylotic myelopathy (CSM). For CSM surgery, it is necessary to evaluate preoperative inter-vertebral disc degeneration (IDD) which determines whether to adopt fusion strategy, and postoperative IDD which is one of the main reasons for reoperation. Modified Pfirrmann grading system is commonly used to evaluate IDD. The objective of this study is to evaluate its reliability and reproducibility on cervical IDD in CSM patients, and to explore its clinical application value. Methods/Design: All 165 patients with CSM were enrolled. 6 physicians (3 spine surgeons and 3 radiologists) who have certain clinical experience were selected. They graded cervical inter-vertebral disc according to modified Pfirrmann grading system, we used intra-class correlation coefficient (ICC) and weighted kappa (wκ) to assess the inter- and intra-observer agreement. After 12 weeks, we repeated the analysis. Results The inter-observer reliability of modified Pfirrmann grading system was excellent with ICC value of 0.76 and near perfect with wκ value of 0.82. The intra-observer reproducibility of modified Pfirrmann grading system was excellent with ICC values ranging from 0.80–0.91, and near perfect with wκ values ranging from 0.83–0.92. Conclusion Modified Pfirrmann grading system has excellent inter-observer reliability and intra-observer reproducibility on cervical IDD in CSM. In addition, it indicates a good appliance among spine surgeons and radiologists, clinical and radiological studies applying it should be deemed accurate. Thus, modified Pfirrmann grading system can be widely used as an appropriate instrument in clinical care.